Ocular drug delivery device

ABSTRACT

An ocular device for insertion into an eye is provided and includes a body having an anterior surface and a posterior surface for placement on one of superior sclera and inferior sclera of the eye. The posterior surface is defined by a base curve that is substantially identical to a radius of curvature of the one of the superior sclera and inferior sclera of the eye. In one embodiment, the ocular device serves as an ocular drug delivery device and contains an active pharmaceutical agent, a lubricant, etc.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/841,357, filed Jul. 22, 2010, which is a continuation of U.S. patentapplication Ser. No. 10/569,743, filed Nov. 9, 2006 (now U.S. Pat. No.8,167,855), which is a national stage of PCT/US04/27510, filed Aug. 25,2004, which claims the benefit of U.S. patent application Ser. No.60/497,831, filed Aug. 26, 2003, each of which is hereby incorporated byreference in its entirety.

STATEMENT REGARDING FEDERAL SPONSORSHIP

The U.S. Government has a paid-up license in this invention and theright in limited circumstances to require the patent owner to licenseothers on reasonable terms as provided for by the terms of Grant No. 2R44 EY 13479.02 awarded by the National Institute of Health.

BACKGROUND

Due to the blood-aqueous and blood-retina barriers, it is difficult toget medicines administrated via the systemic route into the eye itself.Doses large enough to overcome these barriers often result inunacceptable systemic side effects. Virtually all acute and chronicdisease of the eye are therefore treated with medication in the form oftopical eye drop formulations that are applied at least once per day.

In addition to being difficult for patients to insert accurately, theuse of eye drops suffers from two major technical disadvantages, theirrapid elimination from the eye and their poor bioavailability to thetarget tissues. As a result of tear film dilution and elimination andthe permeability barriers of the cornea, typically less than fivepercent of the applied dose of drug reaches the intraocular tissues.Topical ophthalmic pharmaceutical solutions are therefore formulated inhigh concentrations and require frequent dosing. Non-compliance withtreatment, due to required frequency of dosing, lack of detectablesymptom relief in immediate association with treatment application,undesirable systemic side effects due to the need for highconcentrations of drug and other reasons, is a major clinicaldisadvantage.

The idea of placing a solid device into or near the eye to deliver adrug or a lubricant over time is not new. Most recent scientificinterest in this field stems from advances in surgical techniques,pharmacology and pharmacokinetics, as well as the availability ofimproved polymer systems that can be tailored to the specific needs ofocular drug delivery. For clarity, the distinction should be madebetween a device that is “inserted into the eye”, meaning placed underthe eyelids, external to the eyeball itself, and traditionally referredto as an “ocular insert”, vs. a device that is inserted into the eyesurgically, meaning an intraocular insert placed inside the eyeball, orpartly inside the eyeball itself. In fact, some devices are implanted inthe layers of connective tissue forming the globe of the eyeball, andmay even extend through these layers into the eyeball. And some thatcould be inserted topically under the eyelids could also be surgicallyimplanted under the outermost layer, the conjunctiva, anteriorly, orTenon's capsule, posteriorly, and would correctly be referred to assubconjunctival or sub-Tenon's inserts. This would be done via aminimally invasive procedure that does not open into the eyeball itself,but rather into the space currently utilized by ophthalmologists forsubconjunctival or sub-Tenon's injections.

Saettone concisely stated the case for ophthalmic inserts as set forthin the following points: (Saettone, in Chapter 4, Biopharmaceutics ofOcular Drug Delivery, Edman P, ed., CRC Press, London, 1993, 61-79.).

-   -   1. Increased ocular permanence with respect to standard        vehicles, hence a prolonged treatment activity and a higher drug        bioavailability    -   2. Accurate dosing (all of the drug is theoretically retained at        the absorption site)    -   3. Possible reduction of systemic absorption, which occurs        freely with standard eye drops via the nasal mucosa.    -   4. Better patient compliance resulting from a reduced frequency        of medication and a lower incidence of visual and systemic side        effects    -   5. Possibility of targeting internal ocular tissues through        non-corneal (conjunctival-scleral) penetration mutes    -   6. Increased shelf life with respect to eye drops, due to the        absence of water    -   7. Possibility of providing a constant rate of drug release

Prior art has concerned itself with fitting a device under the eyelidinto the conjunctival potential space. The goal to date has been toretain the device in this potential space, or potential pocket, formedby the palpebral portion of the conjunctiva (lining the inside of theeyelid) and the bulbar portion of the conjunctiva (lining the outside ofthe front half of the eyeball). The deeper parts of this potentialpocket are the loose folds of the conjunctiva referred to as theconjunctival formix or conjunctival cul-de-sac. This potential pocket ofcontinuos tissue is limited by the eyelid margins, near the eyelashes,and the corneal limbus, the circle forming the border of the cornea withthe white of the eye. It is referred to as potential space because itnot particularly “designed” to hold anything normally, but rather theexcess tissue allows movement of the eyeball in the orbit and retainsforeign bodies and the tear film from going behind the eyeball into thehead or brain. Being a soft, mucus membrane tissue, the conjunctivaeasily swells in response to allergens or infection. The space itoccupies is therefore potentially expandable by its outward pressure onthe eyelids.

Devices meant to be inserted into this potential space have many shapesand sizes, and are often designed from the engineering standpoint ofease of manufacture (Land D, Benjamin W., Sizes and Shapes ofConjunctival Inserts. ICLC. 21: November/December 212-217, 1994).Resulting shapes are simple, such as oblong rectangular, cylindrical,etc. Their sizes and shapes are predicated on the art of tabletmanufacture and the desire to be inconspicuous in situ. That is, comfortand retention in the conjunctival sac is attained by slipping somethinginto the pocket formed by the conjunctiva lining the eyeball and theinside of the eyelid, and presuming it would be tolerated by the subjectby virtue of its small size. This lack of design specific to thelimiting contours of the intended space leads to discomfort and ejectionof devices of any significant volume. This limitation of overalldimensions in turn significantly restricts the amount of drug they areable to contain and consequently deliver. An example of a commerciallyproduced ocular insert for drug delivery is found in the subject of U.S.Pat. No. 3,618,604, the Ocusert®, assigned to Alza Corporation. Thisproduct was designed from an engineering standpoint of making adrug-releasing “sandwich”. Adequate retention and comfort were assumedby virtue of its small size. Several subsequent patents assigned to AlzaCorporation (U.S. Pat. Nos. 3,416,530, 3,828,777) also describe devicesthat are designed to improve drug delivery kinetics based primarily onmaterial characteristics. These patents address design only in that thedevices are “adapted for insertion in the cul-de-sac of the conjunctivabetween the sclera of the eyeball and the lower lid, to be held in placeagainst the eyeball by the pressure of the lid”. Although they are infact quite small in comparison to the present invention, significantproblems in retention and irritation with the use of the Ocusert®devices are reported in the literature (Sihvola P, et al. PracticalProblems in the Use of Ocusert-Pilocarpine Delivery System. ActaOphthalmol. (Copenh.), 58 (6) 933-937, 1980). In fact, the products haverecently been discontinued, having never been widely accepted or usedclinically.

Another example of prior art that utilizes the potential space of theconjunctival cul-de-sac is that of Benjamin in U.S. Pat. No. 6,217,896.Benjamin, noting the failure to do so in the prior art, proposes tomaximize the use of the actual volume and shape that could be containedin the cul-de-sac, addressing improved conformity, larger drug capacityand increased stability within the sacs. His design is a result ofmaximally filling the potential space of the conjunctival cul-de-sacwith a molding material, and describing the resulting shape obtained.Although his design description includes a back curvature conformingsomewhat to the bulbar surface, this results from his approach ofmaximizing the volume and shape that could be contained in the humanconjunctival sac. The features that he describes as unique to his designare those of the dimensions and volume of the expanded sac itself: “acrescent shape horizontally; a thick inferior horizontal ridge and awedge-like shape sagittally”. The lack of well-defined mathematicaldimensions or expressions for the design, or even a consistentrecommended relationship between the back curvature and the bulbarsurface, confirm his approach of molding the potential space byexpanding it with molding material. As with other prior art, hisinvention is not designed to fit the eyeball itself and fits thepotential space as an empirically derived molded design. Pulling theeyelid away from the globe would result in the insert sliding out ofcorrect position or orientation and/or falling out of the eye.

Another example of prior art that includes a back curvature conformingto the bulbar surface also pursues the engineering approach of fitting adevice into the potential space under the eyelid rather than fitting theeyeball itself. In U.S. Pat. No. 3,416,530, Ness describes an “EyeballMedication Dispensing Tablet”. The hollow chamber of this patent isquite small, in order to comfortably fit in the cul-de-sac.

Much of the prior art depends on material flexibility to achieveretention, without specifying the material of the device or any valuesor ranges for the flexibility claimed. In WO 01/32140 A1 to Darougar,flexibility is claimed in claim 1 as being sufficient to allow bendingalong the curvature of the eye within the upper or lower formix uponbeing positioned, such that the device does not extend onto any visibleportion of the eyeball. The flexibility of Darougar et al is intended toallow entrapment of a long, thin device in the conjunctival folds of theformix, and specifically excludes contact with the eyeball. The scope ofthe design of our invention allows incorporation of materials of anyflexibility.

It is important to note that, other than Benjamin in U.S. Pat. No.6,217,896, the history of the art of ocular inserts for drug deliveryhas been one of creating small devices, designed to be inconspicuous tothe wearer while being trapped in the folds of the conjunctiva orbetween the eyelid and the globe. This has been addressed primarily byvirtue of small size, and secondarily by virtue of shape. Special designfeatures for stability consist of anchors to assist in entrapment, suchas the protrusions mentioned in some prior art, such as WO 01/32140 A1to Darougar, where the protrusions are quite small and are proposed asanchors to assist in entrapment of a long, thin rod-shaped device andrender it undetectable in the conjunctival folds of the formix. Examplesof prior art of considerably small volumes include the Ocusert®described above and the subject of U.S. Pat. No. 3,828,777, whichmeasures at most 5.7×13.4 mm on its axes and 0.5 mm in thickness,yielding 38.5 μl volume. EPA-0262893 to Darougar discloses a rod-likeocular insert device having a volume of 17 μl. These restrictions onvolume significantly limit the amount and subsequent duration ofpractical drug delivery to the eye.

When reviewing the prior art it is evident that the need exists for anocular device that is both stable and comfortable in the eye, yet hasthe volume and mass to deliver therapeutic agents at a controlled rateover an extended period of time.

SUMMARY

The present invention in a first aspect provides an ocular deviceadapted for the controlled sustained release of a therapeutic agent uponapplication onto the upper or lower sclera of the eye, said devicedesigned to fit the sclera of the eye. The ocular device comprises anelongated body of a polymeric material said body containing apharmaceutically active ingredient or a lubricant. The ocular device isfitted to the scleral curvature within the upper or lower formix, uponbeing positioned so that the longitudinal axis of said device isgenerally parallel to the transverse diameter of the eyeball, saiddevice being of a size and configuration such that, upon insertion intothe upper or lower conjunctival area the device does not extend onto anynormally visible portion of the eyeball, i.e., the palpepral aperture.The posterior surface of the device corresponds in a prescribed mannerto the shape of the sclera, in a manner similar to how the posteriorsurface of a corneal contact lens corresponds in a prescribed manner tothe shape of the cornea. The posterior edge of the ocular device can betapered with a radius and a degree of edge lift in a manner similar tothe edges of a corneal contact lens. The anterior surface can bedesigned to interact with the eyelid shape, tension and movement as thedevice occupies the anatomical potential space beneath the eyelid, inorder to provide appropriate positioning, stability, movement andcomfort.

The ocular devices of this invention have been designed to be stable inthe eye and therefore well retained over a prolonged period of time.Additionally, the ocular devices are also designed to provide thepatient with levels of comfort and tolerance not achieved with ocularinserts. The increased comfort, stability and retention of the oculardevices, fitted in the upper or lower conjunctival areas, can be used todeliver therapeutic agents to the eyes via continuous treatment forextended periods of time. One application of the device could be usedfor the singular or periodic treatment or prevention of inflammation,infection or allergy. Repeated applications for up to one to threemonths or longer each can be used for chronic diseases, such asglaucoma. The device may be fitted and removed by the ophthalmictechnician, nurse or doctor, as well as by the patients themselves,following a brief lesson similar to that utilized for contact lens wear.

The ocular device is designed to be placed on the upper or lowerconjunctiva, well within the junction of the palpebral conjunctiva ofthe upper or lower eyelid and the bulbar conjunctiva covering the scleraof the eyeball. Relative to the bulbar conjunctiva, the devices of thisinvention maintain their orientation, and exhibit only minimal movementvertically or laterally, by the pressure and movement of the eyelidagainst the eyeball, or by the movement of the eyeball itself. Slightmovement of the device with blinking and eye movement is advantageous,as with contact lenses, to prevent adherence of the device to the eyeand the associated entrapment of metabolic debris and deposits. Suchmovement relevant to the eyeball of a corneal contact lens is oftenreferred to as “lag”.

The device may include raised areas, acting in use to maintain positionand stability and minimize random movement of the device within theconjunctival area, preferably two raised areas each positioned so as tobe symmetrically disposed about the center point of the body of thedevice.

The ocular device of this invention is designed to fit the sclera of theeye, which has a radius of about 11 mm to about 13 mm. Surprisingly,this radius in the adult population is relatively constant at about 12mm Therefore, the device has an overall, base curve radius of from about11 mm to about 16 mm. Preferably, the device base curve radius is 12 to14 mm. In general, for adults, the area of the sclera limited by theupper formix is greater than the area of the sclera limited by the lowerformix. Thus, an ocular device of the present invention with a length ofup to 35 mm may remain on the upper sclera and one with a length of upto 25 mm may remain on the lower sclera without causing discomfort.

The length of the device of this invention is conveniently from 8 to 35mm for use on the superior sclera to suit the eyes of different sizessuch as infants, children and adults, or from 8 to 25 mm for use on theinferior sclera to suit the eyes of different sizes such as infants,children and adults.

The width (height of the vertical meridian with the device on the eye)of the device of this invention is preferably from about 1.0 mm to 14.0mm to suit the eyes of different sizes such as those of infants,children and adults. The edge of the device of this invention ispreferably tapered and more preferably includes elements of the anteriorand posterior peripheral surface, such as peripheral curve widths andradii and a resultant edge lift and an edge apex contour to optimizecomfort and eyelid interaction.

The volume of the device of this invention can range from about 70microliters to about 400 microliters and is preferably from about 100microliters to about 200 microliters for adults. Infants and childrenunder age five may require a device with a volume below 100 microliters.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

Certain preferred embodiments and modifications thereof will becomeapparent to those skilled in the art from the detailed descriptionherein having reference to the figures that follow, of which:

FIG. 1 is a diagrammatic sectional view of an eye and eyelid;

FIG. 2 is a front elevation view of an ocular drug delivery deviceaccording to a first embodiment;

FIG. 3 is a cross-sectional view taken along the line 3-3 of FIG. 2;

FIG. 4 is a perspective view of an eye with the device of FIG. 1 fittedto the superior sclera;

FIG. 5 is a perspective view of an eye with the device of FIG. 1 fittedto the inferior sclera;

FIG. 6 is a front elevation view of an ocular drug delivery deviceaccording to a second embodiment;

FIG. 7 is a cross-sectional view taken along the line 7-7 of FIG. 6;

FIG. 8 is a cross-sectional view taken along the line 8-8 of FIG. 6;

FIG. 9 is a front elevation view of an ocular drug delivery deviceaccording to a third embodiment;

FIG. 10 is a top plan view of the device of FIG. 9;

FIG. 11 is a cross-sectional view taken along the line 11-11 of FIG. 9;

FIG. 12 is a cross-sectional view taken along the line 12-12 of FIG. 9;

FIG. 13 is a front elevation view of an ocular drug delivery deviceaccording to a fourth embodiment;

FIG. 14 is a cross-sectional view taken along the line 14-14 of FIG. 13;and

FIG. 15 is a cross-sectional view taken along the line 15-15 of FIG. 13.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention incorporates principles that have some basis inrigid gas permeable and soft corneal contact lens design and moreparticularly, the engineering of ocular devices, according to thepresent invention, is particularly suited for producing devices for drugdelivery to the eye while being fitted to the sclera (white) of the eye.Accordingly and as described in great detail below, the device designsdescribed herein address a back central curvature, peripheral curves,edge apex contour, edge lift, overall shape and thickness profilecorresponding to the features of and delimiting aspects of the superiorand inferior sclera, such as the scleral surface curvature, extraocularmuscle insertion points, corneo-scleral junction contour, and thecorresponding eyelid interaction. In complete contrast to prior artdevices and drug delivery approaches, the present ocular devices arespecifically designed to fit the sclera of the eye, with the overallfitting contour accounting for the limiting anatomical features andlandmarks of the sclera, such as the extraocular muscle insertions andlimbal junction with the cornea. The devices are held in place by fluidattraction, and the devices interact with the eyelids, as does a contactlens, for movement, positioning, stability and comfort. The posteriorcontour allows comfortable relative apposition to the scleral surface,and allows movement with blinking and eye movement. The anteriorcontour, edge design and the thickness profile of the embodiments ofthis invention interact with the eyelid both during and between blinksto optimally orient the device in a stable and comfortable position onthe sclera. Each device is inserted by placing it on the inferior orsuperior anterior sclera (white) of the human eye or in treatment ofprimates and quadrupeds, as a contact lens is typically placed on theclear cornea. The design of the device does not require insertion intothe conjunctival cul-de-sac for retention. The design allows the deviceto remain in place even if the eyelid is retracted, just as a contactlens remains in place when the eye is open. This design can be utilizedin its embodiments with a wide range of drugs, lubricants and othermedicinal agents, and with a wide range of potential eroding andnon-eroding drug delivery materials or combinations of materials, suchas via polymer matrix chemistry or reservoir systems. The polymericmaterial of the device may be any polymer that is above its gastransition at 35° C. For example, a silicone elastomer, acrylate, andmethacrylate compositions and hydrogels are suitable. The mechanisms ofthe therapeutic agent or lubricant release may be, for example, bydiffusion through the matrix of the device, by diffusion through anouter wall of the device, osmosis and bioerosion. The design of thedevice allows large volumes of drug to be delivered over a longduration.

With reference to FIG. 1, the following definitions and terms may beuseful regarding the anatomy of the anterior eyeball and the descriptionof the details of the invention. When describing the eye, it isconvention to describe it by using a number of different establishedanatomical terms. FIG. 1 shows an eye 10 that includes a cornea 20 whichis the transparent anterior portion of the eyeball and has a steepercurvature than the rest of the eyeball. The corneal limbus 30 describesan annular border zone between the cornea 20 and the bulbar conjunctiva40 and the sclera 50. The conjunctiva 60 refers to the mucous membraneextending from an eyelid margin to the corneal limbus 30, forming theinner layer of the eyelids and an anterior outer layer of the eyeball.The conjunctival formix 70 is the loose, free conjunctiva connecting theeyelid (palpebral) and eyeball (bulbar) portions of the conjunctivalcul-de-sac 80 which is the potential space between the bulbar andpalpebral conjunctivae and in the conjunctival formix that can expandinto a real space by insertion of a device or other object or substance.The palpebral conjunctivae are supported by the various muscles 90 andembedded glands 92 of the eyelid. As previously mentioned, the sclera 50is the white, opaque outer tunic of the eyeball which covers it entirelyexcept for the segment covered anteriorly by the cornea 20. The sclera50 is in turn covered anteriorly by the conjunctiva 60.

With reference to FIGS. 1-3, FIGS. 2 and 3 generally illustrate anocular drug delivery device 100 that embodies the features of thepresent invention and is constructed for insertion into and wear in theeye 10 by placing it on the inferior or superior anterior sclera (white)50 of the human eye 10 or in treatment of primates and quadrupeds. Thedevice 100 is initially set forth in FIG. 2 in order to define a numberof design terms that help describe the structure and function of all ofthe present ocular drug delivery devices. Thus, it will be understoodand will become more apparent below that the device 100 is merely oneexemplary embodiment of the present invention and in no way is to beconstrued as limiting the scope of the present invention. The device 100includes a body 110 that has an edge apex contour 112 which is theamount and positioning of rounding of the device edges and is typicallydefined as a radius profile swept around a perimeter of the device 100.The device 100 has a base curve 114 which is defined as the primaryradius in each meridian i.e. vertical (axis 3-3) and horizontal (axisH-H), and is the surface of the device 100 that is in contact with thesclera 50 (the posterior surface of the device). In the case where thevalues in each meridian are the same, the base curve 114 is defined as aspherical base curve. In the case where the values in each meridian aredifferent, the posterior surface is defined as a toric posteriorsurface. The device 100 also has an edge lift 116 which is a sectionalgeometry width around the perimeter adjacent to and following the edgeapex contour 112 where the base curve 114 is flatter (increased). Theedge lift 116 is defined by the incremental radius increase and by awidth.

A front curve(s) 118 is defined as the secondary device radius in eachmeridian i.e. vertical and horizontal (axes defined along the body 110).The front curves generate the surface that is in contact with the lid(the front surface of the device). In the case where the values in eachmeridian are the same, the front curve 118 is defined as a spherical. Inthe case where the values in each meridian are different, the frontsurface of the device 100 is defined as a tonic front surface. In apreferred embodiment, the present device 100 disclosed herein, the frontcurves 118 are defined as tonic. The device 100 also includes splines120 which are geometric entities created by polynomial equations, whichdefine smooth blended contour surfaces bridging from one defined shapeor cross-section to another. A lenticular 122 is a manipulation of thethickness of the edge of the device 100 at the front curve geometryadjacent to the edge apex contour 112 on the eyelid side of the device100. A lenticular 122 can be a positive or a negative curve andtypically has a reversed radius direction to the primary front curveradius geometry and the lenticular 122 follows the profile of the edgeapex contour 112, thus providing a reduced thickness cross-sectionprofile around the perimeter of the device 100.

The body 110 of the device is constructed and configured to fit thecontours of the white part (sclera 50) of the eyeball itself, whilepaying tribute to the effects of the eyelids on the position, stability,movement and comfort of the device 100. This fit can be analogized tothe design and fitting of a corneal contact lens over the contours ofthe cornea 20. While the primary function of the contact lens is tooptically correct a refractive error, the lens must also be designed tobe comfortable, stable and non-irritating, and to remain in place inorder to function successfully. Although remaining in place, it alsomust retain a slight movement with eyelid movement and a slight lagbehind movement of the eyeball. This is to permit tear film circulationaround the lens to prevent redness, irritation, adherence to the tissueand build-up of mucus and other surface deposits on the anterior orposterior surfaces. Similarly, an ocular device, such as device 100, fordrug delivery also must exhibit stability of position and yet wouldpreferably retain slight movement and lag for the same reasons. It alsocannot cause excessive awareness or create discomfort as wearing timeproceeds. The interaction with the lid is also determined by the design,and, as with a contact lens, will affect the position, stability,movement and comfort of the device 100. Proper interaction of the device100 with the eyelid also allows flow of the tear film around the device100, which helps keep it clean of mucous build-up that tends to occurwith foreign bodies that are simply trapped in the conjunctivalcul-de-sac 80.

The device 100 of this invention can be worn over the sclera 50 superiorto the cornea 20 as shown in FIG. 4 or inferior to the cornea 20 asshown in FIG. 5. It will therefore be appreciated that all of the oculardrug delivery devices embodying the principals and features of thepresent invention can be positioned in either of these two locations andcan be marked as such.

Contact lens fit and retention depends on the attraction of the deviceto the eye by the surface tension of the tears (fluid attraction), andis assisted by the curvature of the back of the contact lens. Typicallya contact lens has a back curvature corresponding (according torelationships known to those in the art) to that of the cornea, so thatthe lens has a preference for being attracted to the surface of thecornea as opposed to the sclera, or white part of the eye. The generalattraction of the contact lens to the eye is evidenced by the fact thata contact lens does not simply fall out if the wearer tilts the headdown while the eyes are open.

The attraction of the contact lens to a specific part of the eye (thecornea 20) is evidenced by the observation that, with the eye wide open,the lens moves with the eye, such as left, right, up or down with changeof gaze direction. This preferential attraction of the contact lens to aparticular part (shape) of the eyeball, specifically, the more steeplycurved cornea 20 vs. the more flat sclera 50, can be demonstrated if theeye is held open wide and a soft contact lens is dragged from the cornea20 to the white part 50 of the eye, leaving only a small portionremaining over the cornea 20. The contact lens will drift back onto thecornea 20 on its own without a blink as long as the eye remains wetenough. This is because the contact lens is specifically designed, bythe series of posterior base (central) and peripheral curves and thediameter, thickness, etc., to position in close relationship to thecornea 20. In sum, the design and intent of contact lens wearing is toposition the contact lens over the cornea 20 and there is absolutely noteaching or suggestion of placement of the contact lens in anotheranatomical area of the eye 10. In fact, the contact lens is not suitablefor placement in other areas, including the sclera 50 specifically.

Thus, contact lens design and wear is in complete contrast to thepresent invention, where the device 100 is designed to fit the contoursand anatomical features of the white part 50 of the anterior eye, inorder to remain in position on the sclera 50. Currently availablecontact lenses, although designed with several desirable attributes ofocular devices for drug delivery, such as adequate comfort, retentionand movement, do not provide significant drug delivery capability. Thisis due to the inability of the lens materials to deliver drug forsignificantly long duration. Most studies investigating contact lensespre-soaked in drug solutions show release of all of the drug in a matterof hours or perhaps one to two days. The constraints of the contact lensmaterials available having adequate optical clarity (for vision) andoxygen permeability (required for adequate metabolism in the avascularcornea) do not allow high priority in material choice of polymers thatoffer extended drug delivery. Thus, previous drug delivery design whichfocuses on mimicking a contact lens design suffers from a number ofdisadvantages.

The invention disclosed herein is specifically designed to fit thenon-corneal (sclera') anterior surface of the eyeball, remaining outsidethe visual axis and off of the avascular cornea. Therefore, opticaldesign, optical clarity and oxygen permeability are not constrainingparameters to the materials that can be used with the design comprisingthis invention. The device 100 is constructed to be retained at thenon-corneal anterior ocular surface for the topical delivery of drug tothe eye. Contrary to existing ocular drug delivery thought in terms ofthe mechanism of topical drug delivery, the present device 100 isspecifically designed to fit the sclera 50 of the eye 10. This isevidenced by the fact that each embodiment of the present device 100stays on the sclera 50 even if the eyelid is pulled away from the eye10, similar to how a contact lens stays on the cornea 20 while the eyeis wide open. This is a different approach than that of conventionalocular drug delivery design that relies on entrapment of the device inthe folds of the conjunctival sac or between the eyelid and the globefor its retention in position. However, along with retention, the term“fit” in the contact lens field also encompasses positioning, stability,movement, eyelid interaction and even comfort. As with contact lensdesigns, there are specific design features that render the device 100described in this application capable of performing adequately in allthese aspects of “fit”. Due to its design to fit the sclera 50 of theeye 10 and account for dynamic interaction with the movement of the eye10 and of the eyelid, the present device 100 provides comfort in a largedesign. The total device volume can be much greater than device volumein much of the prior art, which is significantly limited by that sizewhich creates detectable sensation or discomfort.

The ocular devices of this invention, in their simplest form, aredesigned to fit the sclera 50 of the eye. Generally, most of the devicesinclude a body that has a generally overall oval shape where thehorizontal dimension is greater than the vertical dimension. This isdepicted in the embodiment shown in FIGS. 6-8, where an exemplary oculardevice 200 is provided. The ocular device 200 has a body 202, a firstend 203 and an opposing second end 205 as well as an anterior surface207 and an opposing posterior surface 209 that are closest to oneanother along a peripheral edge 211 of the body 202.

It is preferred that the shape be symmetrical about a medial axis(vertical meridian) that extends across the width of the body 202 (e.g.,line 7-7 of FIG. 6), such that the lateral halves are mirror images.This aspect allows for the same device design to be used in the rightand left eyes (in the same orientation), and on the superior or inferiorsclera 50 of eye 10. A base curve 212 radius of the device 200 is chosento fit the sclera 50. As best shown in FIG. 7, the body 202 has athickness that is less at its edges 211 and greater toward and includingthe middle of the body 202. More specifically, the body 202 can bedesigned such that it has a maximum thickness at the middle thereof asmeasured from each of the side edges of the body 202 and as a result,the maximum thickness generally lies along the line 8-8 (horizontalmeridian) of FIG. 6. One will appreciate that as a result of thisconfiguration, the thickness of the device 200 continually increasesfrom each side edge toward the middle of the body 202.

In addition, the cross-sectional thickness of the body 202 from thefirst end 203 to the opposing second end 205 is likewise not uniform butinstead tapers inwardly toward each end 203, 205 from the centralsection (middle) of the body 202, as best shown in FIG. 8. In terms of amaximum cross-sectional thickness of the body, as measuredlongitudinally from the first end 203 to the second end 205, thisgenerally lies along the line 8-8 of FIG. 6. The body 202 thus tapers inthe longitudinal direction from its central region toward the ends 203,205 such that the distance between the anterior surface 207 and theposterior surface 209 is at a greatest in the central region, while isat a minimum at the ends 203, 205 and more particularly along theperipheral edge 211 of the body 202. The edge thickness, measured alongthe perimeter edge 211, of the body 202 is generally uniform along theentire perimeter of the elliptical body 202 where the anterior surface207 and the posterior surface 209 meet. Accordingly, this body design ischaracterized as being a significant tonic shape on a fairly sphericalbase curve with a uniform edge radius. In one exemplary embodiment thedevice 200 can have the following dimensions: the width can range fromabout 10 mm to about 25 mm, the height is about 5 mm to about 12 mm andthe cross-sectional thickness (center thickness) is from about 1.0 mm toabout 3.0 mm as measured through the center of the body 202, i.e., alongline 7-7 of FIG. 6. The base curve radius of the device 200 is fromabout 12 mm to about 14 mm When the device 200 has the above dimensions,the volume ranges from about 72 μl to about 400 μl. It will beappreciated that the aforementioned dimensions are merely exemplary innature and do not serve to limit the present invention in any way sinceit is possible for the device 200 to have one or more dimensions thatlie outside of one of the above ranges but still be completely operableas an ocular delivery device.

As previously mentioned, the present inventors discovered that thedevice 200 is particularly suited for and is in face constructed andconfigured for placement on the either the superior sclera as shown inFIG. 4 or the inferior sclera as shown in FIG. 5. Not only is the device200 comfortable to wear in these locations but also it delivers theaforementioned advantageous drug delivery properties that were otherwisenot achievable in conventional ocular devices that were inserted intothe eye 10 and worn at locations other than the sclera 50, such as thecornea 20.

FIGS. 9-12 illustrate an ocular drug delivery device 300 according to asecond embodiment of the present invention. The ocular drug deliverydevice 300 shares a number of similarities to the device 200, such asboth being intended for placement on the sclera 50; however, there are anumber of differences in terms of the construction and design of thedevice 300 compared to the device 200. Similar to the device 200, thedevice 300 has a degree of symmetry in that the device 300 has a body302 that is preferably symmetric about a central axis that is defined asbeing equidistant from a first end 304 and an opposing second end 306 ofthe body 302 and extending between the two sides of the body 302. Thiscentral axis (vertical meridian) is depicted as line 11-11 in FIG. 9. Aswith the device 200, the device 300 includes an anterior surface 301 aswell as a posterior surface 303.

As best seen in the front elevation view of FIG. 9, the device 300generally takes the form of a “dumbbell” with a relatively thin centralsection 308 and two opposing lobe sections 310 formed at ends 304, 306,respectively. The central axis aspect ratio of the lobe 310 to thecentral section 308 (vertical meridian 11-11, as viewed from the frontelevation view of FIG. 9) can vary from about 2:1 to about 10:1. Intheory, the central portion 308 could be infinitely narrow and thin, butincreasingly negative effects on stability and comfort would occur assuch dimensions were approached and therefore, the above ranges, whilenot limiting, serve as a guideline for yielding a suitable device 300.The dumbbell shape of the device 300 redistributes the mass away fromthe center 308 towards the ends 304, 306 of the device 300, and leads todesired positioning on the sclera 50 under the lid and greater stabilityon the eye 10 while maintaining volume.

Increasing the mass in the periphery of the device 300 also takesadvantage of greater scleral surface area available in the forty-fivedegree quadrants vs. the central axis (superior and inferior), which arelimited by the extraocular muscle insertions (superior or inferior rectimuscles). The larger shape of the lobes 310 relative to the centralportion 308, the greater height of the lobes 310 from the surface of theeye and the surface contour of the lobes 310 all contribute to theproper positioning, stability and movement of the device 300 on thesclera 50. Although the lobes 310 can be of any geometrically shapedperimeter, for optimal interaction with the eyelid and the blinkprocess, the perimeter of the lobes 310 distal to the central connectingportion 308 generally has a rounded appearance as viewed in the top planview of FIG. 9, and can have parabolic shapes at the ends 304, 306 withsplines between them. The lobes 310 can be from about 0.5 mm to about 20mm at their greatest diameter. More preferred is a diameter from about 3mm to about 17 mm. Most preferably, the lobes 310 can be from about 7 mmto about 13 mm at their greatest diameter. The center thickness, asmeasured from the anterior surface 303 to the posterior surface 301(similar to the same measurement in a contact lens) of the centralportion 308 of the device 300 can range from about 0.50 mm to about 4.0mm, more preferably from about 0.10 mm to about 2.0 mm, and mostpreferably from about 0.10 mm to about 1.25 mm, while a thickness,measured across a central section, of the lobe 310 can range from about0.5 mm to about 5.0 mm, more preferably from about 0.5 mm to about 3.0mm, to avoid visible bulging through the eyelid, and most preferablyfrom about 0.5 min to about 2.5 mm. The greater thickness and volume ofthe lobes 310 compared to other regions of the body 302 retains adequatevolume for clinical quantities of drug delivery while maintainingposition and stability on the eye through interaction with the eyelid.Keeping the thickness profile of the central portion 308 below that ofthe lobes 310 decreases the potential volume available, but offerssignificant benefits in position, stability, appearance (no bulge notedthrough eyelid) and comfort in the use of the device 300. The nasal andtemporal perimeter (“ends”) 304, 306 of the lobes 310 can approximatecircular, parabolic or elliptical shapes. The transitional curvesbetween the central portion 308 of the device 300 and each of the lobes310 can be linear, parabolic, elliptical or hyperbolic, with splinesbeing preferred, blending to a central cross-section at line-line 12-12.The overall horizontal width of the device 300 can range from about 10mm to about 25 mm, with a base curve radius 314 from about 12 mm toabout 14 mm. The overall volume of the device 300 ranges from about 70μl to about 400 μl. The thickness of the device 300 tapers down to adefined minimum, mostly uniform edge thickness around the entire edgeperimeter 313.

The symmetry of the device 300 about the vertical meridian (axis 11-11(vertical meridian)) is such that the lateral halves are mirror images.This aspect allows for the same device design to be used in the rightand left eyes (in the same orientation) and on the superior or inferiorsclera 50 of the eye 10.

In yet another embodiment that is illustrated in FIGS. 13-15, an oculardrug delivery device 400 is provided. In a number of intendedapplications, the embodiment of device 400 is preferred over the otherprior embodiments (devices 200 and 300) for the reasons set forth above.More specifically, the device 400 is designed to better fit theanatomical features of the eye 10. In this embodiment of the invention,an edge 402 of a central portion 404 thereof that is proximal to thecornea 20 during placement on the eye 10 has a shape correspondingapproximately to a projection of the corneal perimeter. This inwardlycurved shape has a curvature such that if you projected the cornealboundary (at the limbus) and the device 400 boundary into a cornealplane, the device 400 would have an approximately uniform clearance inrelation to the corneal boundary when the device 400 is in its intendedposition on the superior or inferior sclera 50. This feature is termedthe “corneal relief curve” and is generally indicated at 410. Thecurvature of the corneal relief curve in this design is a conic orspline projection of the curvature of the junction of the corneal andsclera (the limbus). Most preferably, it follows a uniform offsetradially from the limbus along the sclera 50. The height difference, asmeasured parallel to 14-14, due to this inward curvature of the centralaxis 14-14 (vertical meridian) between the center of the device 400 andlobe portions 420 can range from about 0.50 mm to about 3.5 mm, and morepreferably, from about 0.50 mm to about 2.5 mm. The “relief contour”provides a shape that will not impinge on the sensitive corneal surface,thereby avoiding effects on comfort and potentially vision, andapproximates a uniform clearance in relation to the cornea 20. The edge406 of the central portion 404 distal to the cornea also has an inwardlycurved shape, with a curvature allowing clearance of the insertion ofthe rectus muscle (superior or inferior, depending upon placement of thedevice on the superior or inferior sclera). This feature is termed a“muscle relief curve” and is generally indicated at 418. The heightdifference, due to this inward curvature, of the central axis 14-14between the center of the device 400 and the lobe portions 420 can rangefrom about 0.15 mm to about 2.5 mm, or more preferably, from about 0.15mm to about 1.5 mm.

Symmetry about the center axis 14-14 (vertical meridian) in FIG. 13 ismaintained in such an embodiment, allowing it to be worn inferiorly orsuperiorly in most cases, but the mass of the central portion 404 isgreater on the side of the longitudinal meridian 15-15 of FIG. 13 thatis distal to the cornea, so that in the superior position, the inwardcurvature 418 of the device 400 clears the superior rectus muscleinsertion, but is less of an inward curvature than that 410 on the sideproximal to the cornea.

The center thickness along line 14-14 (vertical meridian) varies fromabout 0.25 mm to about 3.0 mm according to one embodiment, alongitudinal length of the device 400 measured from end 414 to end 416ranges from about 15 mm to about 22 mm, and the maximum vertical height(as viewed from the side elevation view of FIG. 14) ranges from about 5mm to about 14 mm The distance at the center point across this centralportion 404, from proximal to distal relief curves, along the axis14-14, can vary from less than about 0.5 mm to about 12 mm Morepreferred is the range of from about 1 mm to about 10 mm. Most preferredis the range of from about 6 mm to about 10 mm. The centers of eachdumbbell (each end lobes) 420 on either side of the central portion 404,can range in thickness from about 0.5 mm to about 5.0 mm, morepreferablty, from about 0.5 mm to about 3.0 mm, to avoid visible bulgingthrough the eyelid, and more preferably, from about 0.5 mm to about 2.5mm. The lobes 420 can contain the greater part of the volume of thedevice 400, which ranges from about 70 μl to about 400 μl.

The base curve radius, generally indicated at 412, of the device 400ranges from about 12 mm to about 14 mm.

Each end lobe 420 has a mid-peripheral section 422 that is thinner thanthe peripheral portion of each end lobe 420. This is to mimic the edgeprofile technique typically used in the geometry of a significantly highpowered rigid contact lens. Such high powered lenses have been observedto be most likely of common clinical corneal contact lens designs todislocate from the cornea, due to the interaction with the superioreyelid. The volume of such a contact lens is necessary to provideadequate optics for visual correction Similarly, the volume of thedevice 400 is necessary to provide adequate drug for release. In bothcases, the lenticular feature is a benefit in maintaining position andstability, through interaction with the eyelid, of the device 400 thathas sufficient volume. The lenticular feature yields a transition from apositive front apical curve of the lobe 420 being blended into anegative reverse curve in a range from about 0.5 mm to about 3.5 mm

The symmetry of the device about the axis 14-14 (vertical meridian) issuch that the lateral halves are mirror images. This aspect allows forthe same device design to be used in the right and left eyes (in thesame orientation) and on the superior or inferior sclera of an eye (byrotating 180 degrees in the corneal plane).

In all embodiments, the back surface approximates the primary scleralcurvatures, at least in situ, depending on the flexibility of thematerial. The flexibility of the material utilized to form the devicedetermines how closely the back surface must correspond to the scleralcurvatures prior to insertion of the device. For example, in theory, ahighly flexible material could be made with larger base curve radii, andcould conform in use to form itself to the surface of the sclera. Thisis comparable to the “draping” effect of a soft contact lens on the eye.

The present invention utilizes conformation to the eyeball curvature toestablish the fit against the surface of the eyeball, not to assist withentrapment in the conjunctival folds of the formix. The design of thisinvention aims to provide a surface geometry to fit the sclera 50 of theeye 10 in order to balance comfort and retention with a greater volumeof the device to contain greater amounts of drug for longer delivery tothe eye. Adjusting the base curvature and peripheral curvatures of theposterior surface of this invention allows the use of many materialswith a wide range of flexibility. Such adaptation of design to materialsproperties is well known in the art of contact lens design. A range ofspherical, aspheric and toric back surface base curves, in combinationwith various spherical, aspheric and toric peripheral curve systems,similar to those known in the art of contact lens design, provide theposterior surface that fits against the surface of the eyeball.

Therefore, although a flat posterior surface is within the range ofpossible posterior surfaces of this invention, the preferred range ofvolumes of the device of this invention would result in less of adraping effect and a more limited tendency to conform to the scleralsurface if the posterior surface were flat prior to insertion in theeye, virtually regardless of material utilized. This is comparable to athick soft contact lens, such as a high plus power lens used for thecorrection of aphakia, draping, flexing or bending less on the eye thana very thin, low power soft contact lens. It can be noted analogouslythat even a thin low power soft contact lens, which is quite flexible,is manufactured with a base curvature corresponding somewhat to theocular (corneal) curvature, as opposed to a flat posterior surface, toassist with fitting and draping. In a preferred embodiment of thisinvention therefore, the device would have a posterior surfaceapproximating the scleral curvature.

In fact, the surface of the anterior sclera forms a somewhat tone,asymmetric surface. This would be analogous to fitting a contact lens onthe more asymmetrical mid-peripheral cornea, rather than basing thedesign on a central corneal topography. A back tonic design posterioraspheric surface contact lens would be applicable for use on such atonic surface. A more preferred embodiment would therefore have aposterior surface with an aspheric shape or with two spherical radiithat would allow it to conform to the scleral curvatures. Althoughpotential drug delivery devices with a spherical back surface designwould adequately approximate the scleral surface, the flattening andsteepening of elliptical or aspheric back curvatures would allow finetuning of the movement and tear flow, and hence the optimal fit of thedevice.

Another advantage of specific designs of the back surface of the deviceis to allow uniform tear film flow. More uniform tear flow would allowmore constant release of the drug from the device to the eye. Therefore,although a tonic back surface is not necessary for the more flexiblematerials, it would be preferred for the positioning, stability,comfort, retention and uniform drug delivery with the more rigidmaterials. The most preferred embodiment of this invention thereforecomprises a posterior surface with two elliptical radii that would allowit to conform to the slightly elliptical scleral surface. Theseelliptical radii can result from the manufacturing process or from thein situ conformation of a spherical radii device of flexible materials.The edge lift radii of the peripheral curves 430 can range from 0.0 to5.0 mm flatter than the base curve radii in each meridian. Morepreferred is 0.50 to 5.0 mm flatter than the base curve radii in eachmeridian. Most preferred is from 2.0 to 5.0 mm flatter than the basecurve radii in each meridian. The peripheral curve 430 widths can rangefrom 0.10 to 2.0 mm. More preferred is 0.10 to 1.0 mm. Most preferred isfrom 0.25 to 0.75 mm. The resulting edge profile incorporates theperipheral curvatures 430 of the anterior surface and the posteriorsurface of the device 400.

A contact lens design utilizes lid interaction during the blink and/orinterblink period to optimally position the contact in relation to thecornea. As with a contact lens design, the most preferred embodiments ofthis invention have critical design features of anterior shape, edgecontour and thickness profile that interact with the eyelid, both duringand between blinks, to optimally orient the device in a stable andcomfortable position, in this case on the sclera. An example of such adesign feature of this invention that is well known in the art ofcontact lens design is that of the addition of a minus-carrierlenticular. This design feature affects the edge profile thickness andaffects the interaction with the eyelid. This is known to aid in comfortas well as to stabilize and position the contact lens in the desiredposition on the eye. In a similar manner, the lenticular designs of ourmore preferred embodiments position and stabilize the ocular devices inthe optimal position on the sclera. In fact, it can be observed in theart of contact lens practice that a rigid corneal contact lens with aminus carrier lenticular, if dislocated onto the superior scleraaccidentally, tends to want to remain stable in that position. This isin spite of the other design features of the lens that would tend tohave it return to the cornea. This interaction of a minus-carrierlenticular-type peripheral profile with the eyelid has been utilized inthe most preferred embodiment of the present invention to optimize theposition and stability of the device either in the superior or inferiorposition on the sclera. The more preferred embodiments utilize alenticular on the lobes that is of larger radius than that of thecentral portion of the device. The lenticular radius is thereforesmallest at the central vertical meridian of the device, with the distal(non-corneal) side lenticular radius at that point being closer to thelarger lenticular radius of the lobes and having a larger (approximatelydouble the size) radius than that of the proximal (corneal) side. In thepreferred embodiments of the invention the lenticular is carried all theway around the perimeter of the device to assist in maintaining locationof the device by the lid, balance of position and movement of the devicewith blinking, and minimal awareness of the device or foreign bodysensation with lid movement. The lenticular radii for the distal(non-corneal side) central vertical meridian, proximal (corneal side)central vertical meridian and lobe range respectively from: preferred0.0-5.0, 0.0-5.0, 0.0-5.0 mm; more preferred 0.5-3.5, 0.5-3.5, 0.5-3.5mm; most preferred 1.0-2.0, 0.25-1.5, 1.5-2.5 min. The lenticularenhances balance and minimizes sensation of the device in interactionwith the lid contact area. Stability and retention in the face ofmovement of the superior lid is particularly optimized with the use of alenticular design.

The same elements of design resulting in the overall shape and surfacesand edge geometry of the embodiments of this invention allow thesurgical placement of the device of this invention under the conjunctivaor Tenon's capsule for delivery of drug to the anterior or posterior ofthe eye 10. The overall shape of the preferred embodiments would fitinto position anterior or posterior to a given extraocular muscleinsertion. In the case of being placed posterior to a muscle insertion,the muscle relief curve would maintain its function, while the cornealrelief curve would become an “optic nerve” relief curve. Primarily dueto the curvatures on the anterior and posterior surfaces and the edgeapex contour, there would be minimal structural interference with thetissues surrounding the device of this invention, during surgicalinsertion, wear and surgical removal, if necessary. The maximized volumeof the device as described in each of the present embodiments allowsdelivery of significant quantities of drug in order to minimize thenumber of surgical replacements necessary, yet remain unobtrusive in thenormal movements and sensations of the eye.

The present invention describes the design of an ocular device thatovercomes the deficiencies associated with the conventionally designedocular devices and incorporates one or more of the following features:(a) the ocular device is designed to fit the sclera of the eye; (2) theocular device is designed to be retained on the eye independent of theeyelid; (3) the ocular device is designed to move and position with theblink; (4) the ocular device is designed such that the base curvature ofthe device is spherical, aspherical, or tonic and is defined in relationto scleral anatomical geometry; (5) the ocular device employs one ormore lobes to maximize the mass and volume; (6) the ocular deviceemploys two lobes with greater mass and thickness than the centralconnecting portion (dumbbell shape); (7) the ocular device has a volumefrom about 70 μl to about 400 μl; (8) the ocular device has a lengthfrom about 8 mm to about 35 mm; (9) the ocular device has a height fromabout 1.0 mm to about 14 mm; (10) the ocular device has a thickness fromabout 0.10 mm to about 5.0 mm; (11) the ocular device has a defined edgeapex contour; (12) the ocular device has a defined edge lift; (13) theocular device has a defined front curve(s); (14) the ocular device hasfront curves that are tonic; (15) the ocular device has front curvesthat are aspheric; and (16) the ocular device has a lenticular that isutilized on the front curve geometry.

The present invention can be made in considerably larger dimensions thanis claimed by prior art, and yet still remain stable and comfortable.The consequent volume, shape features and intended use of the devicedesign renders its insertion, in situ evaluation and removal intuitiveto the ophthalmologist, optometrist, other contact lens practitioner,nurse, or ophthalmic technician. The present invention describes adevice that does not need forceps or other instruments or surgicalprocedures for insertion or removal. Patients could be taught to insertand remove such a device, in the manner that they are taught to insertand remove contact lenses. This does not preclude the device from beingplaced underneath the conjunctiva or Tenon's capsule, for example, fordrug delivery to the posterior segment of the eye, in which casesurgical instruments would be involved in the procedure of deviceimplantation.

In one preferred embodiment, the devices are made of non-erodable orerodable materials. Examples of non-erodable materials are, but are notlimited to, polyacrylates and methacrylates, polyvinyl ethers,polyolefins, polyamides, polyvinyl chloride, fluoropolymers,polyurethanes, polyvinyl esters, polysiloxanes and polystyrenes.Examples of erodable materials are cellulose derivatives such asmethylcellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose,hydroxypropyl cellulose and hydroxypropylmethyl cellulose; acrylatessuch as polyacrylic acid salts, ethylacrylates and polyacrylamides;natural products such as gelatin, collagen, alginates, pectins,tragacanth, karaya, chrondrus, agar and acacia; starch derivatives suchas starch acetate, hydroxyethyl starch ethers and hydroxypropyl starchas well as synthetic derivatives such as polyvinylalcohol, polyvinylpyrrolidone, poly vinyl methyl ether, poly ethyleneoxide,neutralized Carbopol®, xanthan gum, polyester, poly ortho ester, polyanhydride, poly phosphazine, poly phosphate ester, poly caprolactone,poly hydroxybutyric acid, poly glycolic acid, poly lactic acid andcombinations thereof.

In another embodiment of the present invention, there is provided amethod of delivering a drug to the eye of an individual in need of suchmedication, comprising the steps of placing the drug into the drugdelivery device and then contacting the individual with thedrug-containing drug delivery device by placing the device on theinferior or superior sclera of the eye. A representative ocular diseaseis glaucoma; those skilled in the art will recognize other diseases,infections or inflammations of the eye that could be treated in thismanner using this invention. The drug delivery devices of this inventionmay contain any of a variety of useful drugs, for glaucoma, allergy,infection, inflammation, uveitis, trauma, post-surgical prophylaxis,pain, dry eye or degenerative conditions. Other agents, such aslubricants, humectants, viscosifiers, demulcants or vitamins, may alsobe delivered with this invention.

In yet another embodiment of the present invention, there is provided amethod of delivering a drug systemically to an individual in need ofsuch medication, that includes the steps of: placing a drug with poorocular absorption kinetics into the drug delivery device and thencontacting the individual with the drug-containing drug delivery deviceby placing the device on the inferior or superior sclera of the eye sothat the drug that is released travels with the tear drainage pathwayinto the naso-lacrimal duct and is absorbed systemically via the nasalmucosa and drainage pathway. A representative systemic disease isdiabetes, and a representative drug is insulin; those skilled in the artwill recognize other systemic diseases, infections or inflammations thatcould be treated in this manner using the present ocular devices.

In another embodiment of the present invention, there is provided amethod of delivering a drug to the eye of an individual in need of suchmedication, comprising the steps of placing the drug into the drugdelivery device and then contacting the individual with thedrug-containing drug delivery device by placing the device on theinferior or superior sclera of the eye posterior to the superior orinferior rectus muscle insertions, below the conjunctiva, intermuscularmembrane or Tenon's capsule, or even into the episcleral space. In thissurgical implantation, the device would still provide a large volume ina shape corresponding to the anatomical potential space of insertion.Movement with eye movement would be limited and less necessary than forembodiments worn on the external eye. The posterior eye would be moreaccessible for drug penetration from this embodiment as placed.Representative ocular diseases are macular degeneration, posterioruveitis, endophthalmitis, diabetic retinopathy, glaucomatous neuropathy;those skilled in the art will recognize other diseases, infections orinflammations of the posterior eye that could be treated in this mannerusing this invention. The drug delivery devices of this invention maycontain any of a variety of useful drugs, for glaucoma, retinopathy,infection, inflammation, uveitis, trauma, post-surgical prophylaxis ordegenerative conditions. In another embodiment of the present invention,there is provided a method of delivering a drug systemically to anindividual in need of such medication, comprising the steps of placingthe drug into the drug delivery device and then contacting theindividual with the drug-containing drug delivery device by placing thedevice on the inferior or superior sclera of the eye. A representativesystemic disease is diabetes; those skilled in the art will recognizeother diseases, infections or inflammations of the body that could betreated in this manner using this invention. The drug delivery devicesof this invention may contain any of a variety of useful drugs, fordiabetes, hypertension, cancer, arthritis, infection, inflammation,various autoimmune diseases, and other systemic pathologies that thatthose skilled in the art of drug delivery will recognize. Other andfurther aspects, features and advantages of the present invention willbe apparent from the following description of the presently preferredembodiments of the invention given for the purpose of disclosure.

The devices of this invention can be fabricated from polymer basedmaterials. The drug or medicinal agent can either be in a dissolved ordispersed state within this polymeric matrix. In one embodiment the drugor medicinal agent is compounded into a preformed polymer where it maybe in the dissolved or dispersed state. The device is then formed formthis drug containing polymer. Examples of useful polymer matrices areethylene vinyl acetate and acrylic based polymer materials. In anotherembodiment, the drug or medicinal agent can be compounded into areactive system. That system may be a monomer or macromer where the drugor medicinal agent is in the dissolved or dispersed state. Polymerizingthe system through UV, visible light, heat or a combination of thesemeans then forms the device. Examples would include the use of liquidacrylic monomers or a reactive silicone pre-polymer.

A preferred manufacturing process for producing the drug deliverydevices of this invention is cast molding. In this process a drug isdissolved or dispersed in a monomer mixture and placed in a plasticcasting mold bearing the geometry of the ocular device. Thermalexposure, UV exposure or a combination of both polymerizes the monomer.The device is then removed from the mold. Post processing may berequired, for example edge finishing. In the case of an ocular devicepolypropylene casting molds are preferred. Most preferred is apolypropylene resin with a melt flow index above 20. One polypropyleneresin is Exxon PP1105E, which has a melt flow index of 34 g/10 min. Withmelt flows above 20 gm/10 min intricately shaped casting molds can beinjection molded with excellent replication of part dimensions.

Post processing is oftentimes required to remove flash and/or to contourthe parting line. For an ocular device, such as contact lenses and thedevices of this invention, the edge profile is critical in providingdevice comfort and fit. The edges of the ocular devices of thisinvention can be shaped and contoured utilizing standard polishingtechniques currently available for rigid gas permeable contact lenses.More preferred is the use of laser edging to form a smooth,well-contoured edge.

Example 1

The aspects of the device of Example One are shown in FIGS. 6-8. Theoverall shape of this invention is greater horizontally than vertically,and can appear as an oval in as shown in the front elevation view ofFIG. 6. It is preferred that the shape be symmetrical about the verticalmeridian, such that the lateral halves are mirror images. This aspectallows for the same device design to be used in the right and left eyes(in the same orientation), and on the superior or inferior sclera of aneye. The base curve 114 radius is chosen to fit the sclera 50. Thecenter thickness is greatest in the horizontal centerline, with taperingto a defined minimal, mostly uniform edge thickness around the entireedge perimeter of the ellipse where the anterior surface 207 andposterior surface, 209 meet. This entails a significantly tone shape ona fairly spherical base curve with a uniform edge radius. Size can rangefrom about 10 mm to about 25 mm in width by about 5 mm to about 12 mm inht by about 1.0 mm to about 3.0 mm center thickness. The base curveradius 114 is from about 10 mm to about 20 mm. The volume of the deviceranges from about 70 μl to about 400 μl. A device in accordance withFIGS. 6-7 was constructed from a silicone elastomer. The dimensions were16 mm in width, 7.0 mm in height and 2.3 mm in center thickness, whichtapered down from the center point. The toric front surface radii were4.0 mm vertical meridian by 9.0 mm horizontal meridian. The base curveradius was 12.4 mm. The device volume was 150 μl.

Example 2

The aspects of the device of Example two are shown in FIGS. 6-8. Thegeneral geometric parameters were discussed in Example One. A prototypedevice was constructed from silicone elastomer. The overall width was21.0 mm, the height was 7.8 mm and the center thickness was 1.5 mm. Thetonic front surface radii were 5.0 mm vertical meridian and 12.0 mmhorizontal meridian. The base curve radius was 12.4 mm. The overalldevice volume was 150 μl. This device was placed on the superior scleraof a subject's eye. The device was stable in the eye with slightrotation observed. The comfort of the device was reported to be good.

Example 3

The aspects of the device of Example Three are shown in FIGS. 6-8. Thegeneral geometric parameters were discussed in Example One. A prototypedevice was constructed from silicone elastomer. The overall width was24.5 mm, the height was 10.0 mm, and the center thickness was 2.3 mm.The toric front surface radii were 6.0 mm vertical meridian by 12.5 mmhorizontal meridian. The overall device volume was 385 μl.

The device was placed on the superior sclera of a subject's eye. Thedevice tended to move slightly to a nasal position. The comfort wasrated at “slight awareness”.

Example 4

The aspects of the device of Example Four are shown in FIGS. 9-12. Theoverall shape is a horizontal “dumbbell” symmetrical about both thecentral vertical axis and the central horizontal axis. A prototypedevice that included the lenticular feature on the anterior geometry ofthe lobes was constructed from silicone elastomer. The distance betweenthe anterior and posterior surfaces, center thickness, (midway betweenthe lobes) was 0.75 mm. The distance between the two surfaces at thecenter of each lobe was 1.5 mm. The anterior curvature at the center ofthe lobe was 4.3 positive radius, transitioning to 2.0 mm negativelenticular radius and then transitioning to a 0.25 positive edge radius.Overall width was 20.5 mm Vertical height was 8.45 mm at its maximum ateach lobe, and 6.5 mm at the center of the device. The back curve radiuswas approximately 12.4 mm. Volume was 130 μl. The lobes could bedetected (cosmetically visible) as slight elevations of the eyelid. Thedevice with the lenticular demonstrated clinically acceptable position,stability and retention, both in the superior and inferior positions.Comfort was quite good, with the exception of some sensation of theedge.

Example 5

The aspects of the device of Example Five are shown in FIGS. 13-15. Aprototype device was made that was overall higher and wider than Example4. This device was 21 mm wide and 7.25 mm height in the center of thedevice. This dumbbell version was 9.5 mm in the dumbbell lobe height asviewed from the front. A uniform spherical 12.4 mm back curvature wasused, as the material used was quite flexible. The indentation distal tothe cornea yielded a 0.26 mm maximum differential in height of thedevice due to this curvature. Device was 2.77 mm from the horizontalmeridian running through the center of the peripheral lobes to the edgeof the device proximal to the cornea. The same measurement from thehorizontal meridian (running through the center of the peripheral lobes)to the edge was 4.47 mm on the side distal to the cornea. We increasedthe front negative lenticular curvature to 2.1 mm. The actual trueradius was therefore 4.0 mm. We smoothed over the transition curves tomake the “bumps” of the lobes less visible under the upper lid duringwear. The width is slightly greater as well. The anterior edge radiuswas decreased, bringing it more into the realm of a contact lens radiusbut the edge lift was the same. The tighter radius is an attempt tolessen the edge sensation from the upper lid, to increase comfort.Volume was 136 μl.

On eye, this device was the most comfortable yet in the superiorposition. No “bumps” were visible under the superior lid. It felt verystable in its interaction the lid. Removal was still relatively easy toaccomplish by massaging the device downward via external manualmanipulation of the eyelid and then removing the device manually, as isdone with a contact lens, once it became visible in the palpebralaperture.

Example 6

The aspects of the device of Example Six are shown in FIGS. 13-15. Aprototype device was cast-molded from an acrylic monomer, with increasededge lift compared to Example 5 due to the addition of a secondaryperipheral curve radius. This device was 21 mm wide and 7.25 mm inheight in the center of the device. This embodiment was 9.45 mm in theheight of the lobe sections as viewed from the front. The horizontalfront curve is a spline that smoothly blends the center and lobe regionsthat have defined vertical front curve radii and edge lift radii andwidths. The front curvature radius in the center axis 15-15 was 7.26 mmcentrally, and 5.09 mm at the lobes. The indentation proximal to thecornea was cut at a lenticular radius of 0.75 mm and yielded a 1.95 mmmaximum differential in height of the device due to this curvature. Thedevice was 2.77 mm from the axis 14-14 running through the center of theperipheral lobes to the edge of the device proximal to the cornea. Theindentation distal to the cornea was cut at a lenticular radius of 1.50mm and yielded a 0.26 mm maximum differential in height of the devicedue to this curvature. The device was 4.47 mm from the axis 14-14running through the center of the peripheral lobes to the edge of thedevice distal to the cornea. The lenticular reverse curve of the lobewas 2.1 mm. The width of the lenticular curve was 1.13 mm proximal tothe cornea and 1.23 distal to the cornea. The edge apex radius was 0.56mm with an edge thickness of 0.43 mm. A toric-12.4 mm vertical meridian(axis 15-15), 12.5 mm horizontal meridian (axis 14-11)—back curvaturewas used since the material was quite flexible. The edge lift base curveradius was 16.4 mm, with a width of 1.0 mm, in the vertical meridiancentrally (15-15), and 16.4 mm, with a width of 1.2 mm, along the entireperiphery at the lobes. The volume was 124 μl. The ocular device of thisExample 6 was cast-molded from an acrylic monomer formulation asfollows. The design of the device was machined into metal molds. Castingmold halves were injection molded from Exxon polypropylene PP1105E.Under an inert atmosphere the lower casting mold half was filled with anacrylic monomer formulation containing a UV initiator. The upper castingmold half was fitted into the lower casting mold half to form the deviceshape. The closed casting mold assembly was placed in a UV curingchamber and exposed to UV at wavelength 365 nm for thirty minutes. Thepolymerized ocular device was then removed. A peripheral curve systemwas molded into the posterior periphery of the device. Their width andtheir incremental increases in radius values define these peripheralcurves over the central base curves. In one embodiment, these values foreach curve can be uniform around the peripheral posterior surface of thedevice. Our most preferred peripheral curve system comprises curves ofdifferent widths in the central and lateral lobe parts of the device.The peripheral curve system provides the edge lift. This approach isutilized in the contact lens art to enhance comfort, movement and tearfilm exchange. When placed on a subject, the device of this Example 6performed as well as that of Example 6 in all aspects, with theadditional results of having increased comfort with little or nosensation of the device in the eye. Lag with eye movement, and movementand repositioning with blink, were excellent. Utilizing a fluorescentdye, a peripheral band of dye under the device, corresponding to theperipheral curve system and its associated edge lift, could be observedin a manner consistent with standard clinical evaluation of such anobservation of rigid contact lenses. The width, evenness, and intensityof this band of fluorescent dye, relative to the fluorescent intensityunder the rest of the device, was judged to be clinically excellentusing criteria practiced by one skilled in rigid contact lens clinicalpractice. All of the designs and methods disclosed and claimed hereincan be made and executed without undue experimentation in light of thepresent disclosure. While, the designs and methods of this inventionhave been described in terms of preferred embodiments, it will beapparent to those skill in the art that variations may be applied to thedesigns and/or methods and in the steps or in the sequence of steps ofthe methods described herein without departing from the concept, spiritand scope of the invention. All such similar substitutes andmodifications apparent to those skilled in the art are deemed to bewithin the spirit, scope and concept of the invention as described bythe appended claims.

1. An ocular device for delivery of a therapeutic agent to the eyecomprising: a preformed body having an anterior surface and an oppositeposterior surface for placement on the sclera of the eye, the posteriorsurface having a preformed curved shape outside of the eye that isdefined by a base curve shaped to fit the sclera; wherein the preformedbody is configured to be held on the sclera such that the preformed bodyis free of contact with and spaced from a cornea of the eye.
 2. Theocular device of claim 1, wherein the posterior surface includes a firstsection that is defined by the base curve and an adjacent second sectionat peripheral edges of the body that is defined by edge lift radii;wherein the posterior surface is shaped to fit the sclera of the eye soas to permit the device to be held on the eye by fluid attraction and beretained on the eye without aid of an eyelid.
 3. The ocular device ofclaim 1, wherein the body includes a central portion with a first edgethat faces the cornea of the eye when the body is placed on the sclera,the first edge having an inwardly curved shape.
 4. The ocular device ofclaim 3, wherein the first edge has a shape corresponding approximatelyto a projection of a corneal perimeter.
 5. The ocular device of claim 3,wherein the central portion includes a second edge, opposite the firstedge, that is further from the cornea when the body is placed on thesclera, the second edge having an inwardly curved shape, the curvatureof the second edge being different than the curvature of the first edge.6. The ocular device of claim 1, wherein the preformed body of theocular device is constructed to be held on a tear film of the sclera byfluid attraction and maintained in a held state thereon such that thepreformed body remains free of contact with and spaced from the cornea.7. The ocular device of claim 1, wherein the posterior surface isconfigured for placement on one of a superior sclera and inferior scleraof the eye.
 8. An ocular device for delivery of a therapeutic agent tothe eye comprising: a preformed body having an anterior surface and anopposite posterior surface for placement on the sclera of the eye, theposterior surface having a preformed curved shape outside of the eyethat is shaped to fit the sclera; wherein the preformed body has one ormore lobes, each lobe having a horizontal width and height greater thana horizontal width and height, respectively, of a peripheral edge of thepreformed body, wherein the increased size of the lobe maintainspositioning and stability of the preformed body on the eye throughinteraction with an eyelid of the eye.